The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors

Background During pregnancy and nursing, a baby's developing immune system is intimately exposed to the mother's antigens. To determine whether this e xposure is of clinical benefit to patients who later receive an allograft a s an adult, we analyzed the outcome of primary renal transplantations from sibling donors. Methods We retrospectively studied graft survival and rejection episodes in 205 patients who had received renal transplants at nine centers between 19 66 and 1996 from sibling donors bearing maternal or paternal HLA antigens n ot inherited by the recipient. The sibling donors were categorized by analy sis of family HLA-typing data. Results In the multicenter analysis, graft survival was higher 5 years and 10 years after transplantation in recipients of kidneys from siblings expre ssing maternal HLA antigens not inherited by the recipient than in recipien ts of kidneys from siblings expressing paternal HLA antigens not inherited by the recipient (86 percent vs. 67 percent at 5 years and 77 percent vs. 4 9 percent at 10 years, P = 0.006 for both comparisons). Paradoxically, ther e was a higher incidence of early rejection in the former group, suggesting that fetal and neonatal exposure to maternal antigens results in immunolog ic priming. Pretransplantation transfusions of donor blood reduced the inci dence of acute rejection while preserving the beneficial effect of toleranc e to noninherited maternal antigens on graft survival. Since 1986, new immu nosuppressive drugs have lessened the shortterm, but not the long-term, sur vival advantage of grafts expressing maternal HLA antigens not inherited by the recipient. Conclusions In the transplantation of a kidney from a sibling donor who is mismatched with the recipient for one HLA haplotype, graft survival is high er when the donor has maternal HLA antigens not inherited by the recipient than when the donor has paternal HLA antigens not inherited by the recipien t. (N Engl J Med 1998;339:1657-64.) (C)1998. Massachusetts Medical Society.